This project has clinical and basic components. We continue in our endeavors to understand the determinants of prognosis in the pediatric non-Hodgkin's lymphomas and to develop improved combination chemotherapy. At the present time our clinical studies are directed towards the utility of colony stimulating factors as a means of increasing dose intensity and ameliorating toxicity in small non-cleaved cell (SNCL) and large cell lymphomas. Our basic studies are directed towards the elucidation of the molecular biology and molecular epidemiology of the SNCL. Major areas of investigation include a) detailed characterization of the non-random chromosomal translocations (particularly 8;14 translocations) associated with the SNCL, with a view to understanding the immediate causes of neoplastic behavior in these tumors and the determinants of geographic and clinical heterogeneity, b) the elucidation of the nature of the association of Epstein-Barr virus (EBV) with the SNCL, c) examination of selected biological and clinical aspects of lymphomas associated with HIV infection; and d) exploration of other molecular abnormalities of potential interest in the SNCL, in particular mutations in p53. Stemming from these studies, we are also investigating the possibility that the molecular abnormalities relevant to tumor pathogenesis (including viral genes) can be used as a target for tumor-specific treatment approaches. We are also undertaking molecular epidemiological studies pertinent to the scl and bcl-2 genes.